gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

11. bis 14.05.2006, Essen

The reversion inducing gene RECK regulates the invasive phenotype of human malignant glioma and serves as a prognostic indicator

RECK (reversion-inducing-cysteine-rich protein with kazal motifs) reguliert den invasiven Phänotyp von humanen malignen Gliomen und dient als prognostischer Marker

Meeting Abstract

  • corresponding author G.H. Vince - Department of Neurosurgery, Julius-Maximilians-University, Wuerzburg
  • C. Hagemann - Department of Neurosurgery, Julius-Maximilians-University, Wuerzburg
  • E. Kunze - Department of Neurosurgery, Julius-Maximilians-University, Wuerzburg
  • I. Lorenz - Department of Neurosurgery, Julius-Maximilians-University, Wuerzburg
  • C. Herbold - Department of Neurosurgery, Julius-Maximilians-University, Wuerzburg
  • K. Roosen - Department of Neurosurgery, Julius-Maximilians-University, Wuerzburg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocFR.03.08

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2006/06dgnc016.shtml

Veröffentlicht: 8. Mai 2006

© 2006 Vince et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: The reversion inducing gene RECK (reversion inducing cysteine rich protein with Kazal motif) uniquely encodes a membrane anchored extracellular protein with protease-inhibitor-like domains. It´s expression is strongly suppressed in hepatocellular most tumors. Restored RECK gene expression reduces the invasive potential. We examined the expression of RECK protein and cell characteristics in human glioma cell lines and studied the effect of RECK expression on patient survival.

Methods: RECK, MMP-2 and MMP-9 expression was detected by RT-PCR, ELISA and immunohistochemistry in GaMG, U251, U373 cell lines and 10 additional primary cell cultures from glioblastoma patients. All cell lines and primary cultures were analyzed by MTT-proliferation test, spheroid drop migration and 3-dimensional collagen gel invasion test with and without Anti-RECK blocking antibody. Additionally, the native tumor tissue of 38 patients undergoing surgery for glioblastoma was examined for RECK expression using Immunohistochemistry.

Results: NIH 3T3 cells showed a strong expression of RECK protein, low levels of MMP-2 mRNA and no MMP-9 protein. The RECK protein levels between glioma cell lines differed considerably and correlated with the expression levels of MMP-9 and MMP-2. No differences were detected in MMP-9 and MMP-2 mRNA levels indicating that the MMP activity seen in immunohistochemistry is the result of posttranscriptional events. Interestingly, TIMP-2 suppression required the presence of RECK. The results of the functional assays correlated with the respective expression of MMP-9 protein in RECK-deficient cells. Thus RECK is a major regulator of MMP-2 and MMP-9 and the malignant phenotype of glioblastoma. In patient tumors low RECK expression levels correlated with lower survival rates. Median survival was 277 days in the low RECK group (n=27) compared to 394 days in the group with high levels of RECK (n=11).

Conclusions: RECK gene is downregulated in human glioma cell lines, primary glioma cell cultures and glioblastoma tissue. Low RECK expression in glioblastoma is associated with worse survival. MMP-9 and to a lesser extent MMP-2 expression is gated by RECK in glioma. The cell biological phenotype of RECK-deficient cells correlates with the respective gelatinase level adding to the understanding of the interaction between RECK expression and MMP activity in malignant glioma. From our data is follows that RECK is a promising therapeutic target.